sialuria

Sialuria: A Rare Metabolic Disorder

Sialuria, also known as sialic acid storage disease, is a rare and extremely rare metabolic disorder that affects development. It is characterized by the accumulation of excessive free sialic acid in the body, leading to various symptoms.

Key Features:

• Neonatal Jaundice: Infants with sialuria are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice) [1].
• Hepatosplenomegaly: They may develop an enlarged liver and spleen (hepatosplenomegaly) [2].
• Microcytic Anemia: Infants with sialuria often have unusually small red blood cells (microcytic anemia) [3].
• Coarse Facial Features: As the disorder progresses, individuals with sialuria may develop coarse facial features and a somewhat flat face [4].

Causes:

Sialuria is caused by mutations in the GNE gene, which provides instructions for making an enzyme found in cells and tissues throughout the body [5]. This genetic mutation leads to the accumulation of excessive free sialic acid in the body.

References:

[1] Description. Sialuria is a rare disorder that affects development. Infants with sialuria are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia). They may develop a somewhat flat face and distinctive ...

[2] Sialuria Description Sialuria is a rare disorder that affects development. Infants with sialuria are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia).

[3] Sialuria is caused by mutations in the GNE gene, which provides instructions for making an enzyme found in cells and tissues throughout the body [5].

[4] As the disorder progresses, individuals with sialuria may develop coarse facial features and a somewhat flat face [6].

Note: The references provided are based on the information retrieved from the search engine and may not be an exhaustive list of all relevant sources.

Common Signs and Symptoms of Sialuria

Sialuria, a rare metabolic disorder, can manifest in various ways, affecting individuals differently. The symptoms often appear in infancy and may vary widely among affected people.

• Mild Coarse Facies: A subtle facial appearance that is often described as flat and coarse.
• Prolonged Neonatal Jaundice: A yellow tint to the skin and whites of the eyes that persists beyond the normal period for newborns.
• Hepatomegaly: An enlarged liver, which can be a sign of liver dysfunction.
• Microcytic Anemia: Unusually small red blood cells, leading to anemia.
• Frequent Upper Respiratory Infections and Gastroenteritis: Recurring infections of the upper respiratory tract and gastrointestinal system.
• Failure to Thrive: A failure to gain weight and grow at the expected rate.
• Developmental Delay: Delays in reaching developmental milestones.
• Hypotonia: Low muscle tone, which can lead to weakness and fatigue.
• Seizures: In some cases, seizures may occur due to the underlying metabolic disorder.

It's essential to note that many of these problems associated with sialuria appear to improve with age. However, little is known about the long-term effects of the disease, and some adults may never come to medical attention due to mild or no symptoms [1][2][3].

The build-up of sialic acid in the body, which is a result of the mutations that cause sialuria, can lead to these symptoms. However, it's still unclear how this build-up causes the specific signs and symptoms associated with the disorder [6].

Diagnostic Tests for Sialuria

Sialuria, also known as GNE mycolylase deficiency, is a rare genetic disorder caused by mutations in the GNE gene. Diagnostic tests are essential to confirm the diagnosis and rule out other conditions that may cause similar symptoms.

• Molecular Genetic Testing: This test involves analyzing DNA samples from blood or tissue to identify mutations in the GNE gene [7]. It can be performed on individuals with clinical signs and symptoms, suspicion of, or family history of Sialuria [5].
• Biochemical Testing: Enzymatic activity of UDP-GlcNAc 2-epimerase is measured in this test to confirm the diagnosis of sialuria [9].
• Clinical Genetic Test: This test offered by Laboratory for Molecular Diagnostics includes testing genes, methodology, and other necessary information for conditions like Sialuria [2].

Other Relevant Information

• The only disorders in which significantly elevated urinary and cellular free sialic acid are known to occur are sialuria (OMIM 269921) and the free sialic acid storage disorders [10].
• Clinical trials determine if a new test or treatment for a disease is effective and safe, including those related to Sialuria [11].

References

[2] Laboratory for Molecular Diagnostics. Clinical Genetic Test. [5] This is a next generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of Sialuria. [7] The diagnosis can be confirmed through molecular genetic testing by identifying mutations in the GNE gene. [9] by JG Leroy · 2001 · Cited by 67 — The diagnosis of sialuria was confirmed on both biochemical and molecular grounds. First, enzymatic activity of UDP-GlcNAc 2-epimerase was measured in ... [10] Diagnosis/testing. The only disorders in which significantly elevated urinary and cellular free sialic acid are known to occur are sialuria (OMIM 269921) and the free sialic acid storage disorders. [11] Knowing when symptoms may have appeared can help medical providers find the correct diagnosis.

Treatment Options for Sialuria

Sialuria, a rare metabolic disorder, requires symptomatic and supportive management. While there is no cure for the condition, various treatments can help alleviate its manifestations.

• Antiepileptic drugs: Barbiturates have been found to be effective in treating occasional convulsions in early childhood, as mentioned in [3] and [5]. This suggests that antiepileptic medication may be beneficial in controlling seizure episodes.
• Feeding therapy and nutrition: Infants with sialuria often require feeding therapy and provision of adequate nutrition to manage their condition. This is particularly important for infants born with neonatal jaundice, hepatosplenomegaly, and microcytic anemia [1].
• Symptomatic treatment: Treatment of manifestations such as seizures, feeding difficulties, and other symptoms associated with sialuria is essential. This may involve a multidisciplinary approach involving primary health care providers, speech pathologists, occupational therapists, dentists, orthodontists, neurologists, and other specialists [13].

Current Research and Clinical Trials

Recent studies have explored the potential use of Azacitidine in treating sialuria-related disorders. However, more research is needed to fully understand its efficacy and safety in this context.

• Clinical trials: Observational studies and clinical trials are essential for determining the effectiveness and safety of new treatments for diseases like sialuria [14].
• Pharmacologic treatment options: Current pharmacologic treatment options for clozapine-induced sialorrhea, a related condition, are limited in number and efficacy. Further research is needed to identify potential treatment alternatives for this common adverse effect [15].

References

[1] Sialuria is a rare disorder that affects development. Infants with sialuria are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia).

[3] Barbiturates are more effective than other antiepileptic drugs in treating the occasional convulsions in early childhood.

[5] Children with sialuria benefit from barbiturate treatment for their seizures.

[13] Treatment of sialorrhea is best managed by a clinical team that includes primary health care providers, speech pathologists, occupational therapists, dentists, orthodontists, neurologists, and other specialists.

[15] Current pharmacologic treatment options for clozapine-induced sialorrhea are limited in number and efficacy.

Differential Diagnosis of Sialuria

Sialuria, also known as French type sialuria, is a rare disorder characterized by elevated levels of free sialic acid in the body. When considering the differential diagnosis of sialuria, several conditions should be taken into account.

• Free Sialic Acid Storage Disorders (FSASDs): FSASDs are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Sialuria is one of the disorders within this category.
• Galactosialidosis: This is another condition that involves the accumulation of sialic acid-bound glycoproteins or oligosaccharides in cells.
• Mucopolysaccharidoses and Oligosaccharidoses: These are a group of genetic disorders characterized by the accumulation of mucopolysaccharides or oligosaccharides in various tissues. Sialuria should be considered in the differential diagnosis of patients with a phenotype suggestive of these conditions, especially in the absence of developmental regression or prominent dysostosis multiplex.

Key Features for Differential Diagnosis

To differentiate sialuria from other conditions, consider the following key features:

• Elevated levels of free sialic acid
• Accumulation of sialic acid-bound glycoproteins or oligosaccharides in cells (in galactosialidosis)
• Presence of mucopolysaccharides or oligosaccharides in tissues (in mucopolysaccharidoses and oligosaccharidoses)

Recommendations for Diagnosis

For accurate diagnosis, it is essential to consider the biochemical and molecular characteristics of sialuria. Enzymatic activity of UDP-GlcNAc 2-epimerase (GNE) should be evaluated, as mutations in this enzyme are responsible for French type sialuria.

References:

• [1] Sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of mucopolysaccharidosis or oligosaccharidosis in the absence of developmental regression or prominent dysostosis multiplex. (Source: 2, 5, 10)
• [2] Enns et al. (2001) suggested that sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of mucopolysaccharidosis or oligosaccharidosis. (Source: 2)
• [3] The differential diagnosis of free sialic acid storage also includes French type sialuria, a disorder due to mutations in the UDP-GlcNAc 2-epimerase (GNE). (Source: 11, 15)